The mechanism and progress of bone healing in humans and other warm-blooded animals are often incomplete or proceed at an unacceptably slow pace. The initial mechanism for the healing of hard tissue (e.g., bone) may generally be characterized as a three-phase process.
The first phase of healing involves the recruitment of the proper types of white blood cells to cleanse the wound and initiate the healing response. To this end, the body seals off blood flow into the damaged area and a white cell type, called neutrophils, secrete toxic superoxide molecules into the area to kill bacteria and induce a general inflammation.
The second phase involves the formation of granulation tissue (i.e., a mixture of fibroblasts, macrophages, and new blood vessels in a loose matrix of collagen and other materials). During this stage of healing, the production of superoxide ion and the inflammatory response is suppressed, while macrophages invade to clean up tissue debris and open a path for mast cells and fibroblasts to follow and secrete angiogenic factors to attract capillary endothelial cells.
Monocytes are also involved, both to secrete fibroblast-activating factors and for conversion to macrophages. Mast cells serve as "helper cells" that amplify new capillary growth. In addition, there is a proliferation of fibroblasts and other cells that secrete the structural protein collagen into the area. There is a migration of chondrocytes and osteoblasts into the healing area to further synthesize bone structural materials.
The third and final stage involves the remodeling and formation of new connective tissue and bone components.
Although there have been a number of substances that are alleged to be capable of inducing cartilage and bone formation, there is a need in the art for compositions and methods which promote the healing of bone and other hard tissue in warm-blooded animals. The present invention provides such compositions and methods, and further provides other related advantages.